4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-(2-pyridinyl)-1H-pyrazole

ABSTRACT

4-(Aryloxyalkyl)pyrazoles of the formula ##STR1## useful as antiviral agents, are prepared by reacting the corresponding diketones of the formula Ar-O-Alk-CH(COR&#39;)COR&#34; with hydrazine or a substituted hydrazine H 2  NNHR. Mono- or bis-pyrazoles are similarly obtained from bis-diketones of the formula ##STR2##

This application is a division of application Ser. No. 008,412, filedFeb. 1, 1979, which is in turn a division of Ser. No. 822,246, filedAug. 5, 1977, now U.S. Pat. No. 4,171,365.

BACKGROUND OF THE INVENTION

(a) Field of the Invention

The invention relates to aryloxyalkylpyrazoles, to the preparationthereof and to compositions and methods for the use thereof as antiviralagents.

(b) Description of the Prior Art

Sterling Drug U.S. Pat. No. 4,031,246, issued June 21, 1977, disclosescompounds useful as pesticidal and antiviral agents and having theformula ##STR3## wherein Ar is phenyl or substituted phenyl, Alk isalkylene of 3-10 carbon atoms and R is lower-alkyl. These compounds areintermediates in the preparation of the compounds of the instantinvention.

Grandberg et al., J. General Chem. of the USSR, 30, 2916-2919(September - December 1960) discloses, inter alia,4-benzyl-3,5-dimethylpyrazole. No biological properties are disclosedfor the latter compound.

SUMMARY OF THE INVENTION

In a composition of matter aspect, the invention relates to4-(aryloxyalkyl)pyrazoles and pharmaceutically acceptable acid-additionsalts thereof, said pyrazoles having the formula ##STR4## wherein Ar isphenyl or substituted phenyl, Alk is an alkylene bridge, and R, R' andR" are selected substituents as defined hereinbelow.

In a further composition of matter aspect, the invention relates tophenylenedioxy compounds of the formulas ##STR5## wherein R is hydrogenor lower-alkyl, R' is lower-alkyl and n is an integer from 3 to 7; andacid-addition salts of said compounds.

In a further composition of matter aspect, the invention relates to acomposition for combatting viruses which comprises an antivirallyeffective amount of a compound of formula I, II or III in admixture witha suitable carrier or diluent.

In a process aspect, the invention relates to a process for preparing acompound of formula I which comprises reacting a diketone of the formulaAr--O--Alk--CH(COR')COR" with a hydrazine of the formula H₂ NNHR.

In a further process aspect, the invention relates to a process forpreparing a compound of formula II or III which comprises reacting abis-diketone of the formula ##STR6## with a hydrazine of the formula H₂NNHR.

In a further process aspect, the invention relates to a method forcombatting viruses which comprises contacting the locus of sid viruseswith an antivirally effective amount of at least one compound of formulaI, II or III.

DETAILED DESCRIPTION INCLUSIVE OR PREFERRED EMBODIMENTS

A preferred aspect of the invention relates to compounds of formula Iabove wherein R is hydrogen, alkyl of 1 to 6 carbon atoms, hydroxyalkylof 1 to 6 carbon atoms, carboalkoxyalkyl of 3 to 6 carbon atoms, orphenyl; R' is alkyl of 1 to 4 carbon atoms or phenyl; R" is alkyl of 1to 4 carbon atoms, phenyl or hydroxy; Alk is alkylene of 3 to 10 carbonatoms optionally interrupted by an oxygen atom separated by at least twocarbon atoms from the terminal bonds of Alk; and Ar is phenyl or phenylsubstituted by from 1 to 3 substituents selected from the groupconsisting of halo, hydroxy, nitro, alkyl of 1 to 4 carbon atoms,lower-alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms,hydroxyalkyl of 2 to 4 carbon atoms, benzyloxy and trifluoromethyl.

Compounds of formula I where the group R is tertiary-amino-lower-alkyl,tertiary-amino-lower-alkanoyl or pyridyl are also within the purview ofthe invention.

In the above general formula I, Alk stands for a saturated aliphatichydrocarbon bridge containing from 3 to 10 carbon atoms. The alkylenebridge may be straight or branched. A preferred class of compounds arethose where Alk is straight chain alkylene of 3 to 10 carbon atoms, andif the Alk bridge is branched, it is preferred that it be symmetrical,that is with the branching at the same relative positions from eitherend of the bridge.

The alkylene bridge, Alk, is optionally interrupted by an oxygen atomseparated by at least two carbon atoms from the terminal bonds of Alk.The oxygen atom is preferably in the center of the alkylene bridge,equidistant from the terminal bonds of Alk.

The carbon chains of R and R' can be straight or branched, thusincluding methyl, ethyl, propyl, isopropyl, butyl, isobutyl,secondary-butyl and tertiary-butyl.

When two or three monovalent substituents are present on the phenyl ringof Ar, they can be the same or different. When halo substituents arepresent, they can be any of the four common halogens, fluoro, chloro,bromo or iodo.

The compounds of formula I are prepared by interacting a diketone orketo-ester of the formula ##STR7## wherein R' is lower-alkyl and R" islower-alkyl or lower-alkoxy, with hydrazine or a derivative thereof ofthe formula H₂ NNHR. The intermediate diketones and keto-esters areobtained as described in copending application Ser. No. 576,311, filedMay 12, 1975, now U.S. Pat. No. 4,031,246, issued June 21, 1977, thedisclosure of which is incorporated herein by reference. The reaction iscarried out by heating the reactants together, preferably at atemperature between about 50° and 100° C. in an inert solvent for aperiod ranging from several minutes to several hours. Stoichiometricallyequivalent amounts of the reactants may be used, although a slightexcess of hydrazine reactant is generally employed.

In the event a keto-ester (R" is lower-alkoxy) is used as the startingmaterial, the alkoxy group is cleaved during the course of the reactionand a compound of formula I wherein R" is OH is obtained.

Alternatively, it is possible to prepare compounds of formula I where Ris alkyl by alkylation of the corresponding compounds of formula I whereR is hydrogen with an alkyl halide in the presence of a strong base,preferably in an inert solvent under anhydrous conditions.

A further aspect of the invention relates to compounds of formulas II orIII, given above, wherein R is hydrogen or lower-alkyl of 1 to 6 carbonatoms; R' is alkyl of 1 to 4 carbon atoms; and n is an integer from 3 to7.

The compounds of formulas II and III are prepared by interacting acompound of formula IV, given above, with hydrazine or a derivativethereof of the formula H₂ NNHR. Substantially equimolar quantities ofbis-diketone IV and hydrazine give a monopyrazole of formula II. The useof two or more molecular equivalents of hydrazine relative to thebis-diketone products a bispyrazole of formula III. The reactionconditions are essentially the same as those used to prepare compoundsof formula I.

The intermediate bis-diketones (IV) are in turn prepared by one of twomethods (a) or (b), as follows:

(a) Interacting hydroquinone with two molar equivalent amounts of acompound of the formula Hal-(CH₂)_(n) CH(COR')₂, where Hal is bromine oriodine, in the presence of a base in an inert organic solvent. Thehaloalkyldiketone reactant is in turn prepared by interacting a dihalideHal(CH₂)_(n) Hal with the alkali metal salt of a diketone, R'COCH₂ COR'.

(b) Interacting a compound of the formula 4-[Hal-(CH₂)_(n) --O]--C₆ H₄--O--(CH₂)_(n) -Hal, where Hal is bromine or iodine, with an alkalimetal salt of a diketone, R'COCH₂ COR', in an inert solvent. Thebis-halide reactant is in turn prepared by interacting hydroquinone withan alkylene dihalide, Hal(CH₂)_(n) Hal.

In the event that acid-addition salts of the compounds of the inventionare prepared and used, the nature of the anion is not critical providedit is relatively non-toxic to mammals and thus pharmaceuticallyacceptable. Such anions include chloride, bromide, iodide, sulfate,nitrate, phosphate, acetate and other alkanoates such as hexanoate andnonanoate; lactate, tartrate, cyclohexylsulfamate and various sulfonatessuch as methanesulfonate, tosylate and naphthalenesulfonate.

The structures of the compounds of the invention were established by themodes of synthesis, by elementary analysis, and by infrared and nuclearmagnetic resonance spectral determinations.

Biological evaluation of the compounds of the invention has shown thatthey possess antiviral activity. They are thus useful in combattingviruses present on inanimate surfaces as well as viral infections inanimal organisms. The in vitro testing of the compounds of the inventionagainst herpes simplex viruses types 1 and 2 and rhinovirus 14 hasshowed that they inhibited viral growth at minimum concentrations (MIC)ranging from about 0.7 to about 50 micrograms per milliliter. The MICvalues were determined by standard serial dilution procedures. In vivoactivity has also been demonstrated in the treatment of mouse genitalherpes simplex type 2 infection.

The antiviral compositions are formulated by preparing a dilute solutionor suspension in an organic or aqueous-organic medium, for example ethylalcohol, acetone, dimethylsulfoxide, and the like; and are applied tothe locus to be disinfected by conventional means such as spraying,swabbing or immersing. Alternatively, the compounds can be formulated asointments or creams by incorporating them in conventional ointment orcream bases, such as alkylpolyether alcohols, cetyl alcohol, stearylalcohol and the like; as jellies by incorporating them in conventionaljelly bases such as glycerin and tragacanth; or as aerosol sprays orfoams. The antivirally effective component of the composition is presentin a concentration of between about 0.7 parts per million and about 5percent by weight, depending upon the chemical species used, the objectto be treated and the type of formulation employed. For disinfection ofinanimate surfaces with aqueous or aqueous-organic solutions,concentrations in the lower part of the range are effective. For topicalapplication in medical or veterinary use in the form of ointment, cream,jelly or aerosol, concentrations in the upper part of the range arepreferred.

The following examples will further illustrate the invention.

EXAMPLE 1 4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole[I; Ar is 2-Cl-4-CH₃ OC₆ H₃, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅].

Hydrazine hydrate (15.7 ml, 0.32 m) was added over a 20 min. period to aslurry of 100 g (0.272 m) of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-heptanedione in 300 ml ofmethanol. The internal temperature rose to a maximum of 50° C. duringthe addition. The reaction mixture was heated at reflux for one hour,and the solvent was then removed in vacuo. The residue was dissolved in300 ml of methylene dichloride and the resulting solution was washedwith three 100 ml portions of water. The organic layer was dried overanhydrous sodium sulfate and the solvent was evaporated to leave 100 gof 4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole as acolorless oil.

The free base thus obtained was dissolved in 250 ml of ethyl acetate andthe solution was treated with a solution of 19.3 ml (0.30 m) ofmethanesulfonic acid in 50 ml of ethyl acetate. The mixture was filteredand colored to 5° C. for two hours. The solid which had formed wascollected by filtration and dried overnight in vacuo at 40° C. to yield105.5 g (84.5%) of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole in theform of its methanesulfonate salt, m.p. 91°-93° C. An additional 14.0 g(11%), m.p. 90°-92° C. was obtained from the mother liquor byevaporation and recrystallization of the residue from ethyl acetate.

A mixture of 18.5 g (0.05 m) of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-heptanedione and 5 ml of 100%hydrazine hydrate in 100 ml of absolute ethanol was heated at reflux forfive hours. The reaction mixture was concentrated in vacuo, the residuedissolved in 50 ml of ethanol, and the solution made acid withhydrochloric acid. The latter solution was concentrated in vacuo and theresidue crystallized twice from an isopropyl alcohol-ether mixture togive 14.5 g of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole in theform of its hydrochloride salt, m.p. 117°-118° C. The correspondinghydrobromide salt had the m.p. 118°-120° C.

A mixture of 18.25 g (0.05 m) of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole in thefree base form and 7.9 g (0.05 m) of nonanoic acid was warmed on a steambath. The reaction mixture was filtered through activated charcoal anddegassed at 50° C. (0.1 mm) to give 12.7 g of the nonanoic acidacid-addition salt of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole as a paleyellow liquid.

Anal. Calcd. for C₂₀ H₂₉ ClN₂ O₂.C₉ H₁₈ O₂ : C, 66.58; H, 9.06; Cl,6.78. Found: C, 66.67; H, 9.00; Cl, 6.89.

4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazolemethanesulfonate when tested in vitro against herpes simplex type 1(herpes 1), herpes simplex type 2 (herpes 2) and human rhinovirus type14 showed antiviral activity at minimal inhibitory concentrations (MIC)of 3-6, 6 and 3 micrograms per milliliter, respectively. The compoundwas also effective in treatment of mice vaginally infected with herpessimplex type 2; survival rates of 80-100% were observed afterintravaginal administration of a 10% aqueous solution of the compound insaturated cotton tampons.

By procedures similar to those used in Example 1, and starting with theappropriate aryloxyalkyl diketone, Ar--O--Alk--CH(COR') COR", andhydrazine or substituted hydrazine, H₂ NNHR, the following compoundswere prepared in yields varying from about 30 to 90 percent.

EXAMPLE 2 4-[6-(4-Methoxy-2-nitrophenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 4--CH₃ O--2--O₂ NC₆ H₃, Alk is (CH₂)₆, R is H, R' and R" areC₂ H₅ ], hydrochloride salt, m.p. 103°-105° C., yellow solid fromacetonitrile; MIC=1 microg/ml (herpes 2).

EXAMPLE 3 4-[6-(2-Chloro-4-nitrophenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--O₂ NC₆ H₃, Alk is (CH₂)₆, R is H, R' and R" are C₂H₅ ], hydrochloride salt, m.p. 130°-132° C., colorless solid fromacetonitrile.

EXAMPLE 4 4-[6-(4-Bromophenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 4--BrC₆ H₄, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅ ], freebase, m.p. 78°-80° C., colorless solid from acetonitrile. Theintermediate 4-[6-(4-bromophenoxy)hexyl]-3,5-heptanedione had the m.p.31°-33° C.

EXAMPLE 54-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-methyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is CH₃, R' and R" areC₂ H₅ ], free base, colorless liquid, b.p. 190°-195° C. (0.01 mm),purified by chromatography on silica with ether; MIC=6 microg/ml (herpes2).

EXAMPLE 64-[5-(2-Chloro-4-methoxyphenoxy)pentyl]-3,5-diethyl-1-methyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₅, R is CH₃, R' and R" areC₂ H₅ ], free base, yellow oil, b.p. 190°-200° C. (0.1 mm), purified bychromatography on silica; MIC=3 microg/ml (herpes 2).

EXAMPLE 74-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-dimethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is H, R' and R" are CH₃], hydrochloride salt, m.p. 150°-151° C., off-white crystals fromacetonitrile; MIC=3 microg/ml (herpes 2).

EXAMPLE 84-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-1,3,5-trimethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Ar is (CH₂)₆, R, R' and R" are CH₃ ],free base, pale yellow oil, b.p. 200°-205° C. (0.03 mm), purified bychromatography on silica; MIC=0.7 microg/ml (herpes 2).

EXAMPLE 94-{2-[2-(2-Chloro-4-methoxyphenoxy)ethoxy]ethyl}-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₂ O(CH₂)₂, R is H, R' and R"are C₂ H₅ ], hydrochloride salt, m.p. 90°-92° C., off-white needles fromethyl acetate; MIC=12 microg/ml (herpes 2).

EXAMPLE 104-[6-(2,5-Dichloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2,5--Cl₂ --4--CH₃ OC₆ H₂, Alk is (CH₂)₆, R is H, R' and R" areC₂ H₅ ], hydrochloride salt, m.p. 148°-150° C., colorless crystals fromacetonitrile.

EXAMPLE 114-[6-(2-Chloro-4-hydroxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--HOC₆ H₃, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅], hydrochloride salt, m.p. 109°-111° C., colorless crystals fromacetonitrile and 2-butanone; MIC=12 microg/ml (herpes 2). The startingmaterial for this preparation was4-[6-(2-chloro-4-benzoyloxyphenoxy)hexyl]-3,5-heptanedione (preparedfrom 2-chloro-4-benzoylphenol and 4-(6-bromohexyl)-3,5-heptanedione).The benzoyl group was hydrolyzed during the procedure.

EXAMPLE 124-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole-1-ethanol

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is CH₂ CH₂ OH, R' andR" are C₂ H₅ ]. The product was distilled at 215°-225° C. (0.05 mm) andchromatographed on silica with ethyl acetate to yield the free base as apale yellow oil; MIC=12 microg/ml (herpes 2).

Anal. Calcd. for C₂₂ H₃₃ ClN₂ O₃ : C, 64.61; H, 8.13; Cl, 8.64. Found:C, 64.77; H, 8.10; Cl, 9.01.

EXAMPLE 13 Ethyl4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazoleacetate

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is CH₂ COOC₂ H₅, R' andR" are C₂ H₅ ].

A mixture of 18.45 g of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-heptanedione, 7.73 g ofcarbethoxymethylhydrazine hydrochloride and 5 g of triethylamine in 100ml of absolute ethanol was heated at reflux for 8 hours. The product wasisolated and distilled to give 16.7 g of ethyl4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazoleacetate asa pale yellow oil, b.p. 205°-210° C. (0.05 mm); MIC=6-12 microg/ml(herpes 1 and 2).

EXAMPLE 144-[5-(2-Chloro-4-methoxyphenoxy)pentyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₅, R is H, R' and R" are C₂H₅ ], hydrochloride salt, m.p. 80°-83° C., colorless solid fromisopropyl acetate; MIC=6-12 microg/ml (herpes 2).

EXAMPLE 154-[4-(2-Chloro-4-methoxyphenoxy)butyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₄, R is H, R' and R" are C₂H₅ ], hydrochloride salt, beige needles from isopropyl acetate; MIC=6-12microg/ml (herpes 2).

EXAMPLE 164-[7-(2-Chloro-4-methoxyphenoxy)heptyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₇, R is H, R' and R" are C₂H₅ ], hydrochloride salt, colorless powder from isopropyl acetate; MIC=6microg/ml (herpes 2).

EXAMPLE 174-[7-(2-Chloro-4-methoxyphenoxy)heptyl]-1,3,5-trimethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₇, R, R' and R" are CH₃ ],chromatographed on silica with ether, and distilled to give the freebase as a pale yellow oil, b.p. 175°-185° C. (0.1 mm); MIC=0.7-1.5microg/ml (herpes 2), 1.5 (herpes 1).

EXAMPLE 184-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-phenyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is C₆ H₅, R' and R" areC₂ H₅ ], chromatographed on silica with chloroform:ether 97:3, anddistilled to give the free base as a yellow oil, b.p. 215°-220° C. (0.05mm); MIC=3 microg/ml (herpes 2).

EXAMPLE 19 4-(6-Phenoxyhexyl)-3,5-diethyl-1H-pyrazole

[I; Ar is C₆ H₅, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅ ],hydrochloride salt, m.p. 119°-121° C., colorless solid from isopropylacetate.

EXAMPLE 20 4-[6-(4-Chlorophenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 4--ClC₆ H₄, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅ ],hydrochloride salt, m.p. 130°-132° C., colorless solid fromacetonitrile; MIC=3 microg/ml (herpes 2).

EXAMPLE 214-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-5-methyl-1H-pyrazol-3-ol

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is H, R' is CH₃, R" isOH].

A mixture of 11.1 g (0.03 m) of ethyl2-acetyl-8-(2-chloro-4-methoxyphenoxy)octanoate, 2.73 g (0.03 m) ofthiosemicarbazide and 1.62 g (0.03 m) of sodium methoxide in 15 ml ofmethanol was heated at reflux for 24 hours. The solid product wascollected, washed with 50% aqueous ethanol and recrystallized fromethanol to give 5.6 g of4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-methyl-1H-pyrazol-3-ol, m.p.145°-146° C.; MIC=6 microg/ml (herpes 2). (During this reaction thethiocarbamyl group (CSNH₂) of the thiosemicarbazide was cleaved so thatthe reaction product is the same as that obtained when unsubstitutedhydrazine is used.)

EXAMPLE 224-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-1-(2-dimethylaminoethyl)-3,5-diethyl-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is CH₂ CH₂ N(CH₃)₂, R'and R" are C₂ H₅ ], free base, yellow oil, b.p. 210°-215° C. (0.03 mm);MIC=6 microg/ml (herpes 2).

EXAMPLE 23 4-[6-(4-Methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole

[I; Ar is 4--CH₃ OC₆ H₄, Alk is (CH₂)₆, R is H, R' and R" are C₂ H₅ ],hydrochloride salt, m.p. 103°-105° C., colorless solid fromacetonitrile.

EXAMPLE 244-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-(2-pyridinyl)-1H-pyrazole

[I; Ar is 2--Cl--4--CH₃ OC₆ H₃, Alk is (CH₂)₆, R is 2-pyridinyl, R' andR" are C₂ H₅ ], free base, pale yellow oil, b.p. 215°-222° C. (0.025mm); MIC=6 microg/ml (herpes 2).

We claim: 1.4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-(2-pyridinyl)-1H-pyrazole.